Reinforcing Effects of Cathinone NPS in the Intravenous Drug Self-Administration Paradigm

Watterson, Lucas R.; Olive, M. Foster

doi:10.1007/7854_2016_33

Cited by 27 publications

(13 citation statements)

References 48 publications

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“…This scenario, in which an unexpected drug is used without knowing its real effects, represents a further risk to the health of people who use illicit substances. Undoubtedly, the pharmacological effects of NPS are frequently much more potent than the drugs they are intended to mimic and this increases the risk of overdose and death .…”

Section: Resultsmentioning

confidence: 99%

On‐site identification of psychoactive drugs by portable Raman spectroscopy during drug‐checking service in electronic music events

Gerace¹,

Seganti²,

Luciano³

et al. 2019

Drug and Alcohol Review

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Introduction and Aims. Hundreds of new psychoactive substances (NPS) have burst into the marketplace, making both the scientific community and people who use drugs lacking of adequate information about their diffusion and effects. In this scenario, drug-checking services have been recently proposed to assist harm reduction policies and provide a global description of the circulating drugs. Design and Methods. The results obtained by a portable Raman spectroscopy device on 472 alleged drugs within the first formal implementation of drug checking in Italy, are reported. The testing was made through a plastic bag held by the applicant and containing the alleged drug. The substance identification was executed by comparison with a spectral library. Results. Illicit substances were detected in 304 samples. Findings included MDMA (106 samples), ketamine (87 samples), cocaine (51 samples), amphetamine (47 samples), methamphetamine (two samples), heroin (two samples) and NPS (nine samples). Two samples were identified as precursors of psychoactive substances. Identification of a noncontrolled substance occurred in 38 samples. Output of inconclusive result was recorded from 128 samples tested on-site, from which the applicant allowed us to collect a small portion in 68 cases, for a delayed laboratory analysis by GC-MS or LC-MS/MS. Discussion and Conclusions. Drug checking by Raman spectroscopy proved effective to identify psychoactive drugs including NPS and track the drug distribution in various recreational settings. The field testing activity revealed the presence of several NPS in the nightlife scenario, often in replacement of traditional illicit drugs, thus posing a high overdose risk and a life-threatening situation. [Gerace E, Seganti F, Luciano C, Lombardo T, Di Corcia D, Teifel H, Vincenti M, Salomone A. On-site identification of psychoactive drugs by portable Raman spectroscopy during drug-checking service in electronic music events. Drug Alcohol Rev 2019;38:50-56]

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Section: Resultsmentioning

confidence: 99%

On‐site identification of psychoactive drugs by portable Raman spectroscopy during drug‐checking service in electronic music events

Gerace¹,

Seganti²,

Luciano³

et al. 2019

Drug and Alcohol Review

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show abstract

“…Drug self-administration is considered the “gold standard” behavioral test for determining the addictive potential of drugs, as most drugs self-administered by laboratory animals are abused by humans [74, this volume] [75]. In the rat drug self-administration paradigm, animals with surgically implanted i.v.…”

Section: Pharmacology Of Mdpv and Its Stereoisomersmentioning

confidence: 99%

Neuropharmacology of 3,4-Methylenedioxypyrovalerone (MDPV), Its Metabolites, and Related Analogs

Baumann

Bukhari

Lehner

et al. 2016

Current Topics in Behavioral Neurosciences

118

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3,4-Methylenedioxypyrovalerone (MDPV) is a psychoactive component of so-called bath salts products that has caused serious medical consequences in humans. In this chapter, we review the neuropharmacology of MDPV and related analogs, and supplement the discussion with new results from our preclinical experiments. MDPV acts as a potent uptake inhibitor at plasma membrane transporters for dopamine (DAT) and norepinephrine (NET) in nervous tissue. The MDPV formulation in bath salts is a racemic mixture, and the S isomer is much more potent than the R isomer at blocking DAT and producing abuse-related effects. Elevations in brain extracellular dopamine produced by MDPV are likely to underlie its locomotor stimulant and addictive properties. MDPV displays rapid pharmacokinetics when injected into rats (0.5–2.0 mg/kg), with peak plasma concentrations achieved by 10–20 min and declining quickly thereafter. MDPV is metabolized to 3,4-dihydroxypyrovalerone (3,4-catechol-PV) and 4-hydroxy-3-methoxypyrovalerone (4-OH-3-MeO-PV) in vivo, but motor activation produced by the drug is positively correlated with plasma concentrations of parent drug and not its metabolites. 3,4-Catechol-PV is a potent uptake blocker at DAT in vitro but has little activity after administration in vivo. 4-OH-3-MeO-PV is the main MDPV metabolite but is weak at DAT and NET. MDPV analogs, such as α-pyrrolidinovalerophenone (α-PVP), display similar ability to inhibit DAT and increase extracellular dopamine concentrations. Taken together, these findings demonstrate that MDPV and its analogs represent a unique class of transporter inhibitors with a high propensity for abuse and addiction.

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“…In abuse liability studies, MDPV produces more robust rewarding effects in the conditioned place preference (CPP) paradigm than amphetamine and is selfadministered at higher rates than cocaine or methamphetamine (Aarde et al, 2013;Schindler et al, 2015). Notably, MDPV potently facilitates intracranial self-stimulation (ICSS) in rats (Bonano et al, 2014;Watterson et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Synthetic cathinone MDPV enhances reward function through purinergic P2X7 receptor-dependent pathway and increases P2X7 gene expression in nucleus accumbens

Gentile

Simmons

Tallarida

et al. 2019

Drug and Alcohol Dependence

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Background and Purpose: Purinergic P2X7 receptors are present on neurons, astrocytes and microglia and activated by extracellular ATP. Since P2X7 receptor activation releases endogenous substrates (e.g., pro-inflammatory cytokines, dopamine, and glutamate) that facilitate psychostimulant reward and reinforcement, we investigated the hypothesis that the synthetic cathinone 3,4-methylenedioxypyrovalerone (MDPV) produces rewarding effects that are dependent on active P2X7 receptors. Methods: Reward function was measured in male mice using intracranial self-stimulation (ICSS). MDPV (0.1, 0.3, 0.5 mg/kg, SC) and a selective P2X7 antagonist (A438079) (5, 10, 50 mg/kg, IP) were tested alone and in combination. In separate mice, gene and protein expression of P2X7 and mitochondrial adenosine triphosphate (ATP) synthase (an enzyme that catalyzes synthesis of ATP, an endogenous ligand for P2X7 receptors) in the nucleus accumbens (NAcc) were quantified following MDPV exposure (0.1, 0.5, 5 mg/kg, SC).

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Reinforcing Effects of Cathinone NPS in the Intravenous Drug Self-Administration Paradigm

Cited by 27 publications

References 48 publications

On‐site identification of psychoactive drugs by portable Raman spectroscopy during drug‐checking service in electronic music events

On‐site identification of psychoactive drugs by portable Raman spectroscopy during drug‐checking service in electronic music events

Neuropharmacology of 3,4-Methylenedioxypyrovalerone (MDPV), Its Metabolites, and Related Analogs

Synthetic cathinone MDPV enhances reward function through purinergic P2X7 receptor-dependent pathway and increases P2X7 gene expression in nucleus accumbens

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